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Identification and Functional Analysis of a Novel CTNNB1 Mutation in Pediatric Medulloblastoma.

Lide AlañaCaroline E Nunes-XavierLaura ZaldumbideIdoia Martin-GuerreroLorena MosteiroPiedad Alba-PavónOlatz VillateSusana García-ObregónHermenegildo González-GarcíaRaquel HerraizItziar AstigarragaRafael PulidoMiguel García-Ariza
Published in: Cancers (2022)
Medulloblastoma is the primary malignant tumor of the Central Nervous System (CNS) most common in pediatrics. We present here, the histological, molecular, and functional analysis of a cohort of 88 pediatric medulloblastoma tumor samples. The WNT-activated subgroup comprised 10% of our cohort, and all WNT-activated patients had exon 3 CTNNB1 mutations and were immunostained for nuclear β-catenin. One novel heterozygous CTNNB1 mutation was found, which resulted in the deletion of β-catenin Ser37 residue (ΔS37). The ΔS37 β-catenin variant ectopically expressed in U2OS human osteosarcoma cells displayed higher protein expression levels than wild-type β-catenin, and functional analysis disclosed gain-of-function properties in terms of elevated TCF/LEF transcriptional activity in cells. Our results suggest that the stabilization and nuclear accumulation of ΔS37 β-catenin contributed to early medulloblastoma tumorigenesis.
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